Learning disabilities are complex developmental disorders of unknown etiology. Genetic influences have been suspected, but the number of genes involved and the magnitude of their influence is unknown. Understanding of the mechanism of genetic influence, and particularly the identification of specific loci involved, could lead to improved understanding of the learning process and better methods of remediation, either through educational strategies or through clinical techniques designed to ameliorate the effects of a particular gene. It has been well established that there is a genetic influence on one form of learning disability, specific reading disability (DeFries, Fulker, and LaBuda, 1987), and possible genetic loci have been localized to chromosomes 15 and 6 (Smith et al., 1989, 1990). However, these linkages have not been confirmed, and this may partially be due to limitations inherent in the family study methodology. Sib pair methods of linkage analysis have strengths that complement the family study methods and make them particularly suitable for the detection of non-Mendelian loci which may influence complex disorders. The purpose of this Project is to establish lymphoblastoid cell lines on the dizygotic twin pairs in which at least one has been identified as having reading or mathematics disability, and their parents. Typing will be done for classical genotyping markers and DNA restriction fragment length polymorphisms. Linkage analysis using different sib pair methods will be used first to test if linkage to the candidate regions of chromosomes 15 and 6 can be detected in this population, and then to localize other genes influencing reading disabilities, mathematics disabilities, or their component skills. The population of twins ascertained and studied as part of the other Projects of this Center constitutes a particularly valuable resource for investigating the genetic influences on learning disability, and the existence of transformed cells will assure that sufficient DNA will be available for these and future genomic studies.